Autism spectrum disorders (ASD) are increasingly recognized, but the mechanisms that lead to the development of these disorders are poorly understood. With the emergence of improved diagnostic measures and genetic technology, the field has realized that phenotypic heterogeneity is largely due to multiple genes. There are few investigators trained to identify phenotypic differences in behavior and physiology within this broad diagnostic spectrum, and even fewer simultaneously trained to integrate this with the study of genetic underpinnings. The candidate has had structured child psychiatry training and will now expand on her research skills through a unique integration of clinical and basic science. The 5 year training proposal (K23) will permit her to develop into an independent clinical investigator by gaining expertise in measuring clinical and neurochemical subphenotypes as well as applying genetic tools to examine associations. The project described below has been designed to develop relevant research skills to bridge interdisciplinary fields under the mentorship of Edwin Cook, Jr., M.D., a clinical research expert in autism and genetics, and C. Sue Carter, Ph.D., a basic science expert in specific neurohormonal measures that have been shown to vary in autism. The principal investigator will study children with ASD by focusing on clinical phenotype, neurochemical measures and genetic associations of related neuropeptide hormones, including oxytocin (OT) which is currently under trial for ASD treatment. Using an existing sample of patients, the investigator will examine whether genes in the OT and vasopressin (AVP) systems are associated with autism overall, and with specific phenotypic subgroups. She will also conduct a clinical study to test the hypothesis that phenotypic differences in peripheral OT levels are related to allelic variance of specific OT pathway processing genes. Over the 5-year training period, 250 outpatient subjects with ASD, ages 5-18 years, will be recruited for diagnostic, OT/AVP blood assay, and genetic pathway testing. They will be an eligible subset of the 650 patients fully assessed by the University of Illinois at Chicago (UIC) Autism Center of Excellence and Simons Genetics Projects. UIC provides an ideal environment for training given the overlap of multidisciplinary expertise and support to establish a program of research within this highly needed scientific interface. [unreadable] [unreadable] [unreadable]